chr6-83125663-C-G

Position:

• chr6-83125663-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015018.4(DOP1A):​c.1649C>G​(p.Ala550Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DOP1A NM_015018.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.35

Genes affected

DOP1A (HGNC:21194): (DOP1 leucine zipper like protein A) Predicted to be involved in Golgi to endosome transport and endoplasmic reticulum organization. Predicted to be located in Golgi membrane. Predicted to be active in endosome and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18075636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOP1A	NM_015018.4	c.1649C>G	p.Ala550Gly	missense_variant	15/39	ENST00000349129.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOP1A	ENST00000349129.7	c.1649C>G	p.Ala550Gly	missense_variant	15/39	1	NM_015018.4	P4
DOP1A	ENST00000369739.7	c.1622C>G	p.Ala541Gly	missense_variant	14/39	1		A1
DOP1A	ENST00000237163.9	c.1622C>G	p.Ala541Gly	missense_variant	15/40	5		A1
DOP1A	ENST00000604380.1	c.401C>G	p.Ala134Gly	missense_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.1622C>G (p.A541G) alteration is located in exon 15 (coding exon 13) of the DOPEY1 gene. This alteration results from a C to G substitution at nucleotide position 1622, causing the alanine (A) at amino acid position 541 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.98
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;.
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Uncertain	0.58	T
REVEL	Benign	0.15
Sift4G	Benign	0.39	T;T;T
Polyphen		0.49	.;P;.
Vest4		0.43
MutPred		0.18		.;Loss of stability (P = 0.0496);.;
MVP		0.093
MPC		0.54
ClinPred		0.92	D
GERP RS		5.1
Varity_R		0.16
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-83835382;